Elgadi K M, Labow B I, Abcouwer S F, Souba W W
Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, 02114, USA.
J Surg Res. 1998 Jul 15;78(1):18-22. doi: 10.1006/jsre.1998.5384.
Acute stresses such as trauma or endotoxemia augment GLN demand and are associated with increased release of this amino acid from skeletal muscle and lung as well as increased expression of glutamine synthetase (GS, the principal enzyme of GLN synthesis) in these tissues. Muscle GLN release is also increased during chronic catabolic states which are associated with depletion of lean body mass, such as starvation or malignancy. We hypothesized that the expression of GS in response to an acute stress would be altered in tumor-bearing rats (TBR) experiencing severe cachexia and therefore a previously heightened GLN demand. Male Fischer 344 rats were implanted with methylcholanthrene-induced fibrosarcoma tumors or underwent sham operations and pair-feeding (sham) with TBR partners. When tumor burden reached approximately 15% of carcass weight, animals received injections of either Escherichia coli lipopolysaccharide (LPS, 1 mg/kg body wt) or saline vehicle. Rats were sacrificed 8 h after injection and lung and muscle tissue were analyzed for GS mRNA and protein via Northern and Western blot techniques, respectively. LPS injection caused an equivalent 4- to 6-fold increase in lung and muscle GS mRNA in both TBR and sham rats (P < 0.01). LPS did not produce a significant increase in GS protein level in muscle tissue of either group or in lung tissue of sham rats. In contrast, endotoxin did lead to a 3.5-fold increase in GS protein levels in lung tissue of TBRs (P < 0.05). This increase in lung GS protein may signify the importance of the lung in maintaining GLN homeostasis during chronic catabolic states where muscle mass is diminished.
创伤或内毒素血症等急性应激会增加谷氨酰胺（GLN）的需求，并与该氨基酸从骨骼肌和肺中的释放增加以及这些组织中谷氨酰胺合成酶（GS，GLN合成的主要酶）的表达增加有关。在与瘦体重消耗相关的慢性分解代谢状态下，如饥饿或恶性肿瘤，肌肉中GLN的释放也会增加。我们假设，在经历严重恶病质并因此先前GLN需求增加的荷瘤大鼠（TBR）中，GS对急性应激的反应表达会发生改变。雄性Fischer 344大鼠被植入甲基胆蒽诱导的纤维肉瘤肿瘤，或接受假手术并与TBR伙伴进行配对喂养（假手术组）。当肿瘤负荷达到胴体重量的约15%时，动物接受注射大肠杆菌脂多糖（LPS，1mg/kg体重）或生理盐水。注射后8小时处死大鼠，分别通过Northern和Western印迹技术分析肺和肌肉组织中的GS mRNA和蛋白质。LPS注射使TBR组和假手术组大鼠的肺和肌肉GS mRNA均等量增加4至6倍（P< = 0.01）。LPS对两组肌肉组织或假手术组大鼠肺组织中的GS蛋白水平均未产生显著增加。相比之下，内毒素确实导致TBR组大鼠肺组织中GS蛋白水平增加3.5倍（P< = 0.05）。肺中GS蛋白的这种增加可能表明在肌肉量减少的慢性分解代谢状态下，肺在维持GLN稳态中的重要性。
